Michael R. Abern

Combination of Penile Traction, Intralesional Verapamil, and Oral Therapies for Peyronie's Disease

Introduction. There is no current consensus as to the most effective non-surgical therapy for Peyronies disease (PD).Aim. To assess the benefit of penile traction therapy (PTT) when added to intralesional verapamil injections (IVI) combined with oral L-arginine 1g bid and pentoxifylline 400 mg tid in men with PD.Methods. 74 men with PD completed 12 IVI. Patients electing to add PTT were advised to wear the device for 2-8 hours daily, and no longer than 2 hours per session. Subjective responses were measured using patient questionnaires. Stretched penile length (SPL) and erect penile curvature (EPC) using penile duplex ultrasound (DU) were measured. Response to therapy was defined as at least a 10 degree reduction in EPC.Main Outcome Measures. Change in SPL (cm), change in EPC (degrees).Results. 39 patients in the PTT group (I) vs. 35 patients in group (II) completed the protocol. 54% of men in group I responded to therapy vs. 46% in group II (p = 0.75). Responders had a mean EPC improvement of 26.9 degrees in group I vs. 20.9 in group II (p = 0.22). Mean PTT use was 3.3 hours per day, and men with >3 hours per day use gained 0.6 cm in SPL vs 0.07 cm using less than or equal to 3 hours per day (p= 0.09), while men in group I on lost 0.74 cm of SPL on average. Multivariate analysis revealed that duration of PTT use significantly predicts length gain (0.38 cm gain for every additional hour per day of PTT use, p = 0.007).Conclusion. There was a trend toward measured curvature improvement, and a significant gain in SPL in men using the combination therapy protocol. Length improvement is related to duration of use of the traction device [corrected].

Delayed radical prostatectomy for intermediate-risk prostate cancer is associated with biochemical recurrence: Possible implications for active surveillance from the SEARCH database

Active surveillance (AS) is increasingly accepted as appropriate management for low‐risk prostate cancer (PC) patients. It is unknown whether delaying radical prostatectomy (RP) is associated with increased risk of biochemical recurrence (BCR) for men with intermediate‐risk PC.

Metformin does not affect risk of biochemical recurrence following radical prostatectomy: Results from the SEARCH database

Background:While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer (PC) incidence, the effect of metformin use on PC outcome is unclear. We investigated the association between pre-operative metformin use, dose and duration of use and biochemical recurrence (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP).Methods:We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with diabetes who underwent RP. Time to BCR between metformin users and non-users, and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic, clinical and/or pathologic features. Time to castrate-resistant PC (CRPC), metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses.Results:Of 371 diabetic men, 156 (42%) were using metformin before RP. Metformin use was associated with more recent year of surgery (P<0.0001) but no clinical or pathologic characteristics. After adjustment for year of surgery, clinical and pathologic features, there were no associations between metformin use (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.61–1.41), high metformin dose (HR 0.96; 95% CI 0.57–1.61) or duration of use (HR 1.00; 95% CI 0.99–1.02) and time to BCR. A total of 14 patients (3.8%) developed CRPC, 10 (2.7%) distant metastases and 8 (2.2%) died from PC. Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95% CI 1.6–16.5), metastases (HR 4.8; 95% CI 1.2–18.5) and PC-specific mortality (HR 5.0; 95% CI 1.1–22.5).Conclusions:Metformin use, dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP. The suggestion that higher metformin dose was associated with increased risk of CRPC, metastases and PC-specific mortality merits testing in large prospective studies with longer follow-up.

Race is associated with discontinuation of active surveillance of low-risk prostate cancer: Results from the Duke Prostate Center

Background:Active surveillance (AS) is increasingly utilized in low-risk prostate cancer (PC) patients. Although black race has traditionally been associated with adverse PC characteristics, its prognostic value for patients managed with AS is unclear.Methods:A retrospective review identified 145 patients managed with AS at the Duke Prostate Center from January 2005 to September 2011. Race was patient-reported and categorized as black, white or other. Inclusion criteria included PSA <10 ng ml−1, Gleason sum ⩽6, and ⩽33% of cores with cancer on diagnostic biopsy. The primary outcome was discontinuation of AS for treatment due to PC progression. In men who proceeded to treatment after AS, the trigger for treatment, follow-up PSA and biopsy characteristics were analyzed. Time to treatment was analyzed with univariable and multivariable Cox proportional hazards models and also stratified by race.Results:In our AS cohort, 105 (72%) were white, 32 (22%) black and 8 (6%) another race. Median follow-up was 23.0 months, during which 23% percent of men proceeded to treatment. The demographic, clinical and follow-up characteristics did not differ by race. There was a trend toward more uninsured black men (15.6% black, 3.8% white, 0% other, P=0.06). Black race was associated with treatment (hazard ratio (HR) 2.93, P=0.01) as compared with white. When the analysis was adjusted for socioeconomic and clinical parameters at the time of PC diagnosis, black race remained the sole predictor of treatment (HR 3.08, P=0.01). Among men undergoing treatment, the trigger was less often patient driven in black men (8 black, 33 white, 67% other, P=0.05).Conclusions:Black race was associated with discontinuation of AS for treatment. This relationship persisted when adjusted for socioeconomic and clinical parameters.

Ketoconazole and Prednisone to Prevent Recurrent Ischemic Priapism

PURPOSE To our knowledge no standard therapy exists for the prevention of recurrent ischemic priapism. We used ketoconazole and prednisone with dosing titrated according to serum testosterone levels to suppress sleep related erections in an attempt to prevent recurrent episodes. MATERIALS AND METHODS Eight patients with recurrent ischemic priapism were treated with ketoconazole and prednisone. Two patients had sickle cell anemia and 6 had idiopathic recurrent ischemic priapism. Testosterone was measured on initial presentation, and ketoconazole and prednisone dosing was titrated to approximately 200 ng/dl testosterone and based on the presence or absence of recurrent ischemic priapism episodes. The International Index of Erectile Function-5 questionnaire was administered to evaluate for erectile dysfunction. Patients were seen monthly and therapy was withdrawn after 6 months. RESULTS Mean testosterone before and after treatment was 468 and 275 ng/dl, respectively. Mean followup was approximately 1.5 years. One patient had 2 recurrent ischemic priapism episodes while on ketoconazole and prednisone treatment. Another patient experienced an increase in testosterone from 361 to 432 ng/dl after initiation of therapy, and 3 recurrent ischemic priapism episodes requiring emergency corporal irrigation. After dose titration testosterone was 184 ng/dl and the patient has had no subsequent episodes. Mean International Index of Erectile Function-5 score was 24.8 points. There were no recurrent ischemic priapism episodes after withdrawal of ketoconazole and prednisone, and no reported symptoms of hypogonadism. CONCLUSIONS Ketoconazole and prednisone therapy was well tolerated in these 8 patients with recurrent ischemic priapism, and with testosterone monitoring and dose titration it was successful in preventing recurrent episodes while preserving sexual function.

Predicting Erectile Dysfunction Following Surgical Correction of Peyronie's Disease without Inflatable Penile Prosthesis Placement: Vascular Assessment and Preoperative Risk Factors

INTRODUCTION Surgical therapy remains the gold standard treatment for Peyronies Disease (PD). Surgical options include plication, grafting, and placement of inflatable penile prosthesis (IPP). Postoperative erectile dysfunction (ED) is a potential complication for PD surgery without IPP. We present our large series follow-up to evaluate preoperative risk factors for postoperative ED. AIMS The aim of this study is to evaluate preoperative risk factors for the development of ED following surgical correction of PD taking into account the degree of curvature, graft size, surgical approach, hypertension, hyperlipidemia, diabetes, smoking history, preoperative use of phosphodiesterase 5 inhibitors (PDE5), and preoperative duplex ultrasound findings including peak systolic and end diastolic velocities and resistive index. METHODS We identified 218 men undergoing either tunica albuginea plication (TAP) or partial plaque excision with pericardial grafting for PD following a previously published algorithm between November 1992 and April 2007. Preoperative and postoperative erectile function, curvature characteristics, presence of vascular risk factors, and duplex ultrasound findings were available on 109 patients. MAIN OUTCOME MEASURES Our primary outcome measure is the development of ED after surgery for PD. RESULTS Ten percent of TAP and 21% of plaque excision with grafting patients developed postoperative ED. Neither curve direction (P = 0.76), graft area (P = 0.78), surgical approach (P = 0.12), chronic hypertension (P = 0.51), hyperlipidemia (P = 0.87), diabetes (P = 0.69), nor smoking history (P = 0.99) were significant predictors of postoperative ED. No combination of risk factors was found to be predictive of postoperative ED. Preoperative use of PDE5 was not a significant predictor of postoperative ED (P = 0.33). Neither peak systolic, end diastolic, nor resistive index were significant predictors of ED (P = 0.28, 0.28, and 0.25, respectively). CONCLUSION This long-term follow-up of a large published series suggests that neither preoperative risk factors nor preoperative duplex ultrasound findings are predictive of postoperative ED, thus reinforcing the use of previously published preoperative treatment algorithms.

The impact of pathologic staging on the long-term oncologic outcomes of patients with clinically high-risk prostate cancer

In the prostate‐specific antigen (PSA) screening era, approximately 15% of US men still present with clinically high‐risk prostate cancer (PC). However, high‐risk PC may be downgraded/downstaged at radical prostatectomy (RP), making additional therapy unnecessary. The authors tested the oncologic outcomes in men with clinically high‐risk disease stratified on RP pathology.

Hyperthermia as Adjunct to Intravesical Chemotherapy for Bladder Cancer

Nonmuscle invasive bladder cancer remains a very costly cancer to manage because of high recurrence rates requiring long-term surveillance and treatment. Emerging evidence suggests that adjunct and concurrent use of hyperthermia with intravesical chemotherapy after transurethral resection of bladder tumor further reduces recurrence risk and progression to advanced disease. Hyperthermia has both direct and immune-mediated cytotoxic effect on tumor cells including tumor growth arrest and activation of antitumor immune system cells and pathways. Concurrent heat application also acts as a sensitizer to intravesical chemotherapy agents. As such the ability to deliver hyperthermia to the focus of tumor while minimizing damage to surrounding benign tissue is of utmost importance to optimize the benefit of hyperthermia treatment. Existing chemohyperthermia devices that allow for more localized heat delivery continue to pave the way in this effort. Current investigational methods involving heat-activated drug delivery selectively to tumor cells using temperature-sensitive liposomes also offer promising ways to improve chemohyperthermia efficacy in bladder cancer while minimizing toxicity to benign tissue. This will hopefully allow more widespread use of chemohyperthermia to all bladder cancer patients, including metastatic bladder cancer.

African-American men with low-grade prostate cancer have higher tumor burdens: results from the Duke Prostate Center.

Background:To investigate racial differences in tumor burden (cancer volume, cancer percentage and cancer to PSA ratios) in a large cohort of men undergoing radical prostatectomy (RP).Methods:Demographic, clinical and pathological data of patients undergoing RP between 1993–2010 were reviewed and compared between African-American (AA) and non African-American (nAA) men. Further assessments of pathological tumor burden (estimated tumor volume, percent of cancer involvement, and estimated tumor volume/PSA ratios) were performed across Gleason score categories.Results:Of 4157 patients in the analysis, 604 (14.5%) were AA. Overall, AA patients were younger, had higher Gleason scores, PSA levels and incidence of palpable disease (all P<0.001). Despite comparable prostate weights (39.4 vs. 39.6 g), AA men had higher percent cancer involvement and estimated tumor volume (all P<0.001) but similar estimated tumor volume/PSA ratios (P>0.05). When stratified by Gleason scores, prostate weights were comparable; however, estimated tumor volume, percent cancer involvement and estimated tumor volume/PSA ratios were higher in AA men with low grade (⩽6) prostate cancer (PCa), similar in intermediate grade (7–8) and lower in high grade (9-10) PCa compared to nAA men.Conclusions:In this large series, AA patients had higher disease burden (estimated tumor volume, percent cancer involvement, estimated tumor volume/PSA ratios) compared to nAA but this association was especially pronounced in low grade (Gleason ⩽6) cancers. These data depict a complex picture of relations between race and tumor burden across the spectrum of PCa aggressiveness. Further investigation is warranted to understand the mechanisms of racial disparities in PCa.

Focal Therapy of Prostate Cancer: Evidence-based Analysis for Modern Selection Criteria

Focal therapy for prostate cancer has been increasingly utilized with the goal of effective disease control while maximizing patient functional outcomes. The optimal patient selection criteria are not known and therefore are not standardized. This review compares the available expert panel consensus guidelines with the selection criteria utilized in recently published focal therapy trials. Because the data from focal trials are still maturing, the currently enrolling clinical trials are reviewed as well. In addition, the recent literature regarding technological advances in prostate biopsy and imaging strategies are added to the current guidelines to recommend a rationale for patient selection.